The central theme of this application is the synthesis of chiral molecular receptors designed to show high enantiomeric specificity in complexation. In systematic studies, the multiple interaction modes at the origin of chiral recognition in biological and chemical systems will be analyzed. To define the principles of chiral molecular recognition in aqueous solution, a series of water-soluble optically active cyclophane hosts with C2-symmetry, derived from a novel versatile chiral spacer unit, are prepared. Enantiomeric guests with an apolar moiety and a pi-acceptor site will be recognized differentially by hosts providing a combination of apolar binding, pi-pi electron donor-acceptor, and steric interactions. Ionic guest enantiomers will be separated by complexation to hosts providing apolar, steric, and lateral ion pairing interactions in a hydrophobic local environment. Systematic studies within a series of related host and guests will clarify the contribution of each interaction mode to the overall degree of binding and to the degree of chiral efficiency. Hosts with high enantiomer differentiation potential will be immobilized on polymeric supports, and the efficiency of the resulting novel chiral stationary phases in chromatographic resolutions will be explored. Alternatively, alpha-amino acids, alpha-arylpropionic acids, alkaloids, and other chiral biologically relevant compounds and drugs will be resolved on the preparative scale through diastereomeric complex formation in crystallization, distribution, and transport processes. Part II of the application proposes the synthesis of the first chiral molecular receptors designed for the specific complexation of mono-and oligosaccharides. Studies with these novel receptors will define the hitherto unexplored factors that are important in carbohydrate recognition. A receptor for beta-glucose with enantiomeric and anomeric specificity in binding will be prepared. The more favorable diastereomeric complex will be stabilized by four hydrogen bonds between glucose hydroxyl groups and hydrogen bond acceptor centers of the receptor. Comparisons of the binding strengths in the series of diastereomeric complexes formed by all eight aldohexoses will provide important information on the minimum interaction requirements for monosaccharide binding and on the relative strength of hydrogen bonds formed by an anomeric, a primary, or a secondary sugar hydroxyl residue as donor-group. For the chiral recognition of oligosaccharides, an entirely novel class of highly preorganized receptors, the helicopodands, will be prepared. These non-macrocyclic receptors ("podands") possess C2- symmetry and are structured by a rigid helicene ("helico") backbone which defines at the two ends of a complete helical turn an asymmetric cleft aligned with hydrogen bond donor and acceptors sites. Oligosaccharides, e.g. gentiobiose, bind to the cleft by a combination of multiple van der Waals contacts and hydrogen bonds. The role of solvation in carbohydrate binding will be explored, Systematic modeling studies of carbohydrate recognition will advance the molecular understanding of the factors that are important in protein-carbohydrate interactions, in cell-cell and in cell-virus recognition; they also will provide a more rational design of saccharide-based viral inhibitors.